title: Novel somatic frameshift mutations of genes related to cell cycle and DNA damage response in gastric and colorectal cancers with microsatellite instability.
abstract: OBJECTIVE
  Microsatellite instability (MSI) in sporadic gastric cancer (GC) and colorectal cancer (CRC) causes frameshift mutations in gene sequences that contribute to cancer pathogenesis. Many mutations have already been identified in these two cancer types, but some are still undiscovered.
  
  
  METHODS
  We analyzed seven genes (cell cycle control and DNA damage signaling/repair-related genes) with seven or more mononucleotide repeats in 30 GC samples with high MSI (MSI-H), 15 GC samples with low MSI (MSI-L), 45 GC samples that were microsatellite stable (MSS), 33 CRC samples with MSI-H, 15 CRC samples with MSI-L, and 45 CRC samples that were MSS. Single-strand conformation polymorphism (SSCP) and DNA sequencing were used for the analysis.
  
  
  RESULTS
  We found somatic frameshit mutations of the KNTC1 (6.7% GC, 12.1% CRC), ZC3H13 (3.3% GC, 15.2% CRC), CENPH (6.7% GC), TOPBP1 (3.0% CRC), NDCO80 (3.0% CRC), RIF1 (6.7% GC), and NBS1 (3.3% GC, 3.0% CRC) genes in the cancers with MSI-H. Mutations were detected in MSI-H, but not in MSI-L or MSS samples.
  
  
  CONCLUSIONS
  Novel frameshift mutations occurred in seven genes in GC and CRC with MSI-H. The results of our study suggest that the mutations might contribute to the development of GC and CRC with MSI by deregulation of the cell cycle and DNA damage signaling/repair.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Yoo Ri
authors.initials: YR
authors.lastname: Kim
authors.forename: Nak Gyun
authors.initials: NG
authors.lastname: Chung
authors.forename: Mi Ran
authors.initials: MR
authors.lastname: Kang
authors.forename: Nam Jin
authors.initials: NJ
authors.lastname: Yoo
authors.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
mesh_terms: D044466:Asian People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D003598:Cytoskeletal Proteins; D004249:DNA Damage / Q000235:genetics*; D017931:DNA Primers; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D016368:Frameshift Mutation; D006801:Humans; D053842:Microsatellite Instability; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D016601:RNA-Binding Proteins; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D034501:Telomere-Binding Proteins / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C489309:KNTC1 protein, human; D008869:Microtubule-Associated Proteins; C112156:NBN protein, human; C120529:NDC80 protein, human; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C492743:Rif1 protein, human; C110513:TOPBP1 protein, human; D034501:Telomere-Binding Proteins; C556840:ZC3H13 protein, human; C068688:centromere protein E